Hydroxytyrosol protects retinal pigment epithelial cells from acrolein-induced oxidative stress and mitochondrial dysfunction.

Abstract

Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 μmol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required > 75 μmol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 μmol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration.

• Authors: Zhongbo Liu, Lijuan Sun, Lu Zhu, Xu Jia, Xuesen Li, Haiqun Jia, Ying Wang, Peter Weber, Jiangang Long, Jiankang Liu
• Journal: Journal of neurochemistry (J Neurochem) Vol. 103 Issue 6 Pg. 2690-700 (Dec 2007) ISSN: 1471-4159 [Electronic] England
• PMID: 20938484 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Coloring Agents
• Indicators and Reagents
• NF-E2-Related Factor 1
• NFE2L1 protein, human
• Neuroprotective Agents
• Oxidants
• Tetrazolium Salts
• Thiazoles
• 3,4-dihydroxyphenylethanol
• Acrolein
• Superoxide Dismutase
• Glutathione Transferase
• thiazolyl blue
• Glutathione
• Phenylethyl Alcohol
• Calcium

Topics

• Acrolein (antagonists & inhibitors, toxicity)
• Antioxidants (pharmacology)
• Calcium (metabolism)
• Cell Line
• Cell Survival
• Coloring Agents
• DNA Damage
• Glutathione (metabolism)
• Glutathione Transferase (metabolism)
• Humans
• Indicators and Reagents
• Macular Degeneration (pathology)
• Mitochondria (drug effects, metabolism)
• NF-E2-Related Factor 1 (biosynthesis)
• Neuroprotective Agents
• Oxidants (metabolism)
• Oxidative Stress (drug effects)
• Phenylethyl Alcohol (analogs & derivatives, pharmacology)
• Protein Carbonylation (drug effects)
• Retinal Pigment Epithelium (cytology, drug effects)
• Superoxide Dismutase (metabolism)
• Tetrazolium Salts
• Thiazoles